N-(2-Methyl-6-benzoxazolyl)-N′-15-n aphthyridin-4-yl urea (SB334867) a hypocretin receptor-1 antagonist preferentially prevents ethanol seeking: comparison with natural reward seeking

摘要

Orexins/hypocretins (Orx/Hcrt) are hypothalamic peptides that regulate a wide range of physiological processes and have been shown to be recruited by drugs of abuse. This study was designed to test the effect of the specific Orx/Hcrt receptor-1 (Hcrt-r1) antagonist SB334867 on reinstatement elicited by ethanol (EtOH)-associated stimuli vs. stimuli associated with a conventional reinforcer (i.e., SuperSac: consisting to 3% glucose and 0.125% saccharin w/v). SB334867 (1–10 mg/kg, IP) dose-dependently reduced reinstatement induced by the EtOH- but not SuperSac-associated stimuli. These findings support a differential role of Hcrt-r1 in mediating EtOH seeking vs. natural reward seeking.